The invention is generally in the field of tissue engineering, more specifically in the field of growth and conditioning of tissue constructs. With the American public aging and sports-related injuries increasing, the demand for orthopedic surgeries has grown tremendously. In 1998, there were over 3 million people afflicted with such problems in the United States alone, representing both a significant clinical problem and commercial opportunity. Currently, a great deal of research is being devoted to restoring function in damaged orthopedic tissues. Restoration of function to damaged orthopedic tissues has taken many forms: autografts, allografts, xenografts, implantable (permanent and biodegradable) biomaterials, and tissue-engineered constructs. Each of these treatments has achieved some degree of success, but each has its limitations.
Two of the more attractive solutions which have recently emerged are allografts and tissue-engineered constructs. An allograft is a tissue transplanted between individuals of the same species. Allografts relieve some of the burden of a supply source, while tissue-engineered constructs can in theory be a complete off-the-shelf solution. Tissue engineering of cartilage constructs grown in vitro has emerged as a potentially more suitable treatment than allografts. However, either of these solutions will prove to be commercially viable only if the construct or allograft can restore function. Restoration of function is more likely if the implanted tissue possesses: 1) an active cellular component to facilitate remodeling, 2) similar biomechanical properties to sustain load-bearing movements, and 3) an ability to properly integrate into the host tissue for a sustained, long-term maintenance of function.
The orthopedic tissues in the body receive biomechanical stimulation; in particular, long bones, articular cartilage, and the meniscus are constantly being loaded. Prior to implantation in the body, ex vivo cultured tissues often lack the proper mechanical properties or cellular function to become fully integrated and functional. One approach to improving this deficiency is to subject the tissue to similar biomechanical loads as seen in situ, such as shear stress, prior to implantation. Reduced cellular function may also be addressed through exposure to biochemical stimuli such as growth factors. A combination of biochemical and biomechanical stimuli may be most desirable.
Integration of a construct may be better if it is heterogeneous; that is, the type of cells or characteristics of the cells varies across the construct. For example, a construct could have cartilage-like tissue on one side and bone-like tissue on the other side. Mimicking the native tissue heterogeneity in this way may accelerate the repair of defects involving tissue interfaces such as osteochondral defects.
Functional tissue engineering of cartilage involves the use of bioreactors designed to provide a controlled in vitro environment that embodies some of the biochemical and biomechanical stimuli known to regulate chondrogenesis. Various types of bioreactors have been investigated for use in producing tissue-engineered human cartilage, including rotating-wall vessels, spinner flasks, perfusion, and compression/perfusion bioreactors. In each type of reactor the flow of the culture medium causes the growing tissue to experience a different dynamic environment, potentially influencing the character of the final tissue. Three main types of forces are currently used in cartilage-culturing processes: hydrostatic pressure, direct compression, and shear fluid environments.
Prior art bioreactors provide the cells or construct with a single culturing or conditioning environment. It would be advantageous to have a bioreactor wherein biochemical and biomechanical stimuli can be applied to each side of a construct. Such a bioreactor, where the biochemical and biomechanical stimuli are different on each side, could result in a heterogeneous construct. Thicker constructs could result with the use of the same stimuli applied to both sides of the construct.